UCSB researchers discover breakthrough on replacement organs

UC Santa Barbara researchers have discovered a way to manipulate cells in embryos in a breakthrough that may help scientists grow laboratory body parts to replace hearts, kidneys or other organs damaged by disease or injury.

Working on a microscopic worm that has helped spawn a half-dozen Nobel Prizes, scientists learned they can block formative signals that dictate whether a cell becomes skin tissue, intestines, pancreas or anything else. A cell's destiny — what developmental biologist Joel Rothman calls its "profession" — could be changed.

"We can switch them into something else," he said, adding it's still unknown whether the discovery will translate to humans. But if it does, it could help bring new ways of dealing with car accidents that crush organs, skin cancer or a disease that renders a liver useless.

"If we want to make kidneys out of them, we can make kidneys," he said. "If we want to make skin cells, we can. We can essentially make replacement parts."

The discovery, published in the journal Genes & Development, comes out of five years of research on trying to determine how the fate of cells is finalized. By studying mutated cells and what's missing from them, researchers in Rothman's lab figured out how to block messages called notch signals, named for the indentation in the wings of fruit flies.

The signals are sent to embryonic cells and to undeveloped cells in adults. Soon after the message is sent, a cell's pathway to becoming an organ or skin tissue is finalized.

"They've committed to their profession," Rothman said. "They refuse to undergo a career change."

Researchers discovered they could make the cells change their destinies and become something else when they changed or eliminated the gene that transmits the notch signal.

They did their work on a 1,000-cell worm known as C. elegans. The same kind of organism has been used by other teams in Nobel Prize-winning studies, including a technique that enables scientists to turn off genes such as those linked to cancer and other diseases.

Now the Santa Barbara team will likely pass its discovery on to other researchers. The next studies could involve blocking notch signals in mice. If it works in mice, the chance of success is high for humans.

It would mean scientists could manipulate cells in a laboratory so they would develop into skin tissue, organs and almost any other body part. People with failed kidneys would have options other than dialysis or transplants.

"Will it be a decade or five decades? I don't know, but we will be able to replace virtually any part of our body," Rothman said. "I'm completely confident we will be able to do this. The timeline is what I don't want to be pinned down on."

The possibilities also excite Dr. Vincent Fortanasce. But one thing stops the Arcadia neurologist, who serves on the board of the National Catholic Bioethics Center: the possibility that human embryos would be destroyed.

"Our belief is that we protect life from the very beginning to the very end," he said, adding the objection would disappear if cells that were not reproductive cells from a human embryo were used for new organs.

The Santa Barbara research focused on embryonic cells, but Rothman said a single embryonic cell could possibly be used without harming the embryo or changing its ability to develop into a fetus. He said it's also possible that blocking notch signals would work in adult cells. That could mean cells from a person with heart disease could be used to grow a new, healthy organ with zero chance of rejection.

"It would be perfectly matched," he said. "An ultimate goal is to be able to do this without embryos."

Other interested observers focused on the potential for treating disease and injury.

"If you can grow organs to replace a damaged pancreas in a diabetic ... I think that would be fantastic," said Dr. Ronald Chochinov, a Ventura endocrinologist, comparing the possibility to current treatment. "Everything else is patchwork."

As far as the possibility of growing replacement body parts, Rothman characterized his research and similar work as taking a natural process and tweaking it.

"We have done it since early in human history," he said, referring to things such as the breeding of animals and changes made in the way crops are grown. "We have been manipulating other creatures on this planet for 100,000 years."